Composition, comprising hydrofluoric acid, for inhibiting dental erosion

ABSTRACT

The present invention relates to a composition, for inhibiting dental erosion, and the use thereof. The composition comprises an aqueous solution of hydrofluoric acid, in which the concentration of hydrofluoric acid is 0.05%-2.00% and the pH is between 2.5 and 4.5.

The present invention comprises a composition for inhibiting dentalerosion, a process for preparing a composition for inhibiting dentalerosion and use thereof.

BACKGROUND OF THE INVENTION

The present invention relates to oral compositions which containfluoride in suitable concentrations. It has surprisingly been found thatdiluted hydrofluoric acid applied on dental hard tissues at pH 2.5-4.5reduce their solubility to up to 90%, when these are subsequentlyexposed to erosive acids. The oral compositions of the present inventionare thus formulated to reduce solubility of teeth and prevent or stop,development of dental erosions.

Dental erosions represent loss of dental hard tissues (enamel, dentineand cementum) presumably due to excessive consumption of acidicbeverages, juices or fruits. In some cases concerning subjects witheating disturbances, strong acid from the stomach may reach the oralcavity and cause severe dental erosions. Food and beverages may containor weak inorganic acids which may provide a pH as low as 3 or less, onthe tooth surfaces, whereas the strong acid from the stomach may yield apH at 1.5 or below.

Teeth are very strong and resistant against mechanical wear, butdissolves and lose their integrity at pH levels below pH 5.5. Dentalerosions are related to dental caries, which also is caused by organicacids. However, in the case of caries the organic acids are formed insmall amounts by bacteria located on the tooth surfaces (bacterialplaque) during metabolism of dietary carbohydrates, in particularsucrose. The carious lesions formed are in areas which are usuallycovered with dental plaque (i.e. along the gingival margin, aproximallyand in occlusal fissures. The caries process is progressing slowly andis caused by small amounts of acids. pH levels below 5.5 are known tocause cavities over time, and in dental cementum the “critical pH” is ashigh as pH 6. This is due to the chemical properties of cementum, whichcontains more carbonate than enamel, and thus has a higher solubility.The caries process produce cavities (i.e. localized loss of hard tissueunderneath dental plaque, whereas dental erosions involve loss of harddental tissue over whole surfaces. Dental erosions are caused by acidsoriginating from the diet (or from the stomach) and involves mostfrequently the lingual and buccal aspects of the incisors, and theocclusal surfaces of molars, mainly the mandibular molars.

Dental caries was previously a major public health problem in theindustrialized world. The use of fluoride prophylaxis, mainly in theform of fluorinated toothpaste, has improved the situation markedly, anddental caries is now mainly found in high risk groups, which constituteabout 10% of the population in the industrialized world. Dental erosionsare on the other side, found in large numbers of teenagers, that consumehigh amounts of acidic beverages. It appears that some individuals havehigher resistance against these challenges than others, and allindividuals with high consumption of acidic beverages do not contractdental erosions. Fluoride toothpaste and other conventional methodsdesigned to stop dental caries, are not effective against dentalerosions. The mechanism of the inhibition of caries by fluoride, is nowwell understood. It was originally thought that fluoride worked solelyby reducing the solubility of enamel at the pH related to dental caries(pH 5.5-4.5). However, it is now realized that fluoride works mainly byre-mineralization. If fluoride ions are available in the plaque during apH challenge in plaque, the calcium and phosphate released from theplaque become supersaturated with respect to fluorapatite (withcontribution by the fluoride ions in plaque), and this solid phase isre-deposited on the tooth surface, thus eliminating the loss of mineral.However, this re-mineralization can only occur at pH above 4.5 andconventional fluoride methods are thus not effective concerning dentalerosions which originate at pH levels below 4.5, as discussed above.

THE RELATED ART

In prior art fluoride methods are with few exception, designed asprophylaxis for dental caries. At a certain time it was believed thatfluoride inhibited caries by reducing the solubility of dental enamel.

It has now been convincingly demonstrated that this is not an importantaspect of the mechanism of fluoride in caries prophylaxis. It was shownthat shark enamel, which consists of solid fluorapatite, was showingcaries lesions when introduced in the human oral cavity, in, in situexperiments in high caries challenge regimen. Many experiments have beenperformed to reduce enamel solubility, usually at pH 4.5. Anotherfrequently used experimental design was to measure acquisition offluoride on the surface and in the depth of dental enamel. However, itwas observed that no relationship existed between the acquisition ofsurface fluoride by a method, and its clinical effect (Murrey). It wasreported that an acidulated phosphofluoride preparation was able todeposit high amounts of fluoride in the enamel surface, but nocorresponding convincing improved caries inhibition was experienced,although some positive results were reported. However, no reference wasgiven to a composition for inhibiting dental erosions. This problem waspreviously related to people (mostly farmhands) that worked on orange orlemon plantations and were supposed to eat large quantities of suchfruits.

Stannous fluoride represents a special case. It was observed thatstannous fluoride in toothpastes and in aqueous solution reduced thesolubility of enamel at pH 4.5 (U.S. Pat. No. 2,946,725) and this wasthought to be caused by the low pH of the toothpaste, which were due tostannous ions being hydrolized by for nation of SnOH and liberation ofH⁺. Stannous pyrophosphate was added as an extra source of Sn⁺⁺ ions. Aclaim of the patent above was that slightly soluble stannous compoundsshould be added to the toothpaste to obtain a pH between 3.5 and 6. Noreference was made to dental erosions. Stannous fluoride toothpastes arestill in use but they suffer from stability problems concerning bothfluoride and stannous ions, and dental staining is a problem in even newand improved product (Perlich 1995).

In vitro studies showed that solutions of stannous fluoride showeddecreasing pH upon storage, and that lowered pH reduced the solubilityreduction of enamel (Muhler J.dent Res.). Buyilkyilmaz et al. (1997)reported that pre-treatment of teeth with 1-4% aqueous solutions oftitanium tetrafluoride inhibited the solubility of enamel inhydrochloric acid. The effect was suggested to be due to formation of atitanium containing “glaze” on the surface of the enamel. U.S. Pat. No.5,004,597 represent an improvement where the stability of fluoride andstannous ions in toothpaste are improved. A stannous fluoride containingtoothpaste which claims to be able to reduce the development of dentalerosions (Solidox syreblokk), has recently been introduced on theNorwegian marked. However, stannous fluoride preparations have certaindisadvantages; their shelf life are limited (due to oxidations ofstannous ions), stannous fluoride is expensive, and dental stain isknown to develop in some cases during long-term use of stannousfluoride. Titanium tetra fluoride is very expensive, and aqueoussolutions exhibit a low pH and contain very high amounts of fluoride.None of these references disclosed teach & composition for inhibitingdental erosion and use thereof with diluted hydrofluoric acid of a pHbetween 2.5 and 4.5 as active agents against dental erosions.

NO 155225 B describes attempts to reduce the erosive potential of citricacid and citric acid containing beverages by adding fluoride tobeverages.

Hughes, J. A. et al. “The protective effect of fluoride treatmentsagainst enamel erosion in vitro.” J. of Oral Rehabilitation. 2004. 31;357-363 describes the effect of addition of sodium fluoride to citricacid- or citric acid based drinks, on the erosion, and also by severalcommercial fluoride products. The authors found a slight effect byadding fluoride to citric acid or corresponding beverages, but thesedifferences were not statistically significant. The acidulated gel whichshowed some beneficial effect on erosion, had a pH of 5.15, and can thusnot relate to the present patent application. Citric acid with additionof fluoride was not significantly different from citric acid withoutfluoride (Table 3). The paper cites a paper by Larsen and RichardsCaries Res 2002: 36-73: Fluoride is unable to reduce dental erosionsfrom soft drinks. This paper supports the findings in D2. The presentauthors conclude in their discussion “differences in erosion betweenwith and without fluoride were small and most did not achievestatistical significance”

Van Rijkom, H. et. al. “Erosion-inhibiting effect of sodium fluoride andtitanium tetrafluoride treatment in vitro.” Eur. J. Oral Sci. 2003.111;253-257 concerns the erosive inhibiting effect of 1% neutral NaFtreatment and a 4% solution of TiF4. Bovine teeth were pre-treated witheither NaF or TiF4 and then exposed to 50 mM citric acid which containedcalcium and phosphate and had a pH of 3. The results showed that the NaFreduced the mean lesion depth from 4.5 um to 3.5 um after 30 min ofexposure, whereas TiF4 caused a reduction to 2.7 um. This is a moderateinhibition considering the mild erosion regime used. The differenceswere however statistically significant. TiF4 is an agent of academicinterest, but it has no practical use due to a very high prize. The TiF4is furthermore very hygroscopic and difficult to handle. Solutions ofTiF4 have a pH of about 1.5.

Sorvari, R. et. al. “Effect of fluoride varnish and solution on enamelerosion in vitro.” Caries Res. 1994. 28; 227-232 examine the effect of24 h treatment with 1.2% NaF and of the commercial varnish Duraphat, onthe hardness of enamel after subsequent exposure of the enamel samplesby a cola-drink of pH 2.6 for 4 min. Both treatments improved thetreatment compared with an untreated control. To expose teeth for 1.2%F− for 24 h is not a practical procedure, but is theoreticalinteresting. The effect should be seen in the light of the very lighterosive power of a cola drink and the short exposure time.

U.S. Pat. No. 2,946,725 deals with toothpaste formulations concerningstannous fluoride-containing pastes and is thus not related to thepresent patent application. The pH of the pastes is also not relevant,as it relates to pH caused by hydrolysis of stannous ions and not byaddition of diluted hydrofluoric acid.

SUMMARY OF INVENTION

Dental erosions are caused by acid-containing fruits and drinks.Traditional caries preventive measures including use of fluoride, arenot effective against dental erosions. The invention, involves use ofdiluted hydrofluoric acid, which is a weak acid with a pK_(a) of 3.45.Pre-treatment of teeth with such acid in concentrations of 0.1-1%, hasbeen shown to be able to protect tooth mineral against erosive acids.This effect is probably associated with the presence of un-dissociatedHF which is abundant in aqueous solutions of hydrofluoric acids, inparticular below the pK_(a) of such acids.

Un-dissociated HF is thought to be able to get in contact with themineralized tooth surface and thus get closer to this surface than anycharged species of fluoride. It is thereby able to form erosionresistant products on the tooth surface which do not form in the absenceof un-dissociated HF. This species is probably able to transfer fluorideto the mineral surface with a minimum of exposure free protons, whichcan cause damage to such surfaces. The invention can be used in productdesigned to enhance the resistance of teeth against erosive acids suchas mouth rinses, gels and toothpastes.

The present invention is based on a new method by which the solubilityof teeth is reduced and thus improved, beyond what is possible by use ofthe methods outlined above. It has now been discovered that dilutedaqueous solutions of hydrofluoric acid reduces the solubility of dentalof teeth against erosive acids, markedly, without having any of thedisadvantages connected with the above methods.

The present invention comprises a composition for inhibiting dentalerosion comprising aqueous solution of hydrofluoric acid in aconcentration of 0.05%-2.00% with a pH between 2.5 and 4.5. The saidcomposition comprises at least one of a humectant, a binder, athickening agent, one or several abrasive agents, a liquid phaseincluding a humectant, a surfactant and flavour. The abrasive agent isany one of silica, xerogels, hydrogels and aerogels. The abrasive agentis silica in a concentration of 3-75% by weight. The liquid phase of thepresent invention comprises said humectant in a concentration of 10-90%by weight of the composition. The humectant is chosen from cellulose,xanthan gum, sorbitol, glycerol, propylene glycol, polypropylene andpolyethylene glycol. The binder and said thickening agent is any one ofsodium carboxymethyl cellulose, hydroxyethyl cellulose, xanthan gumfinely divided silica, Irish moss and synthetic hectorities in aconcentration of 0.5-10% by weight of the composition. The compositioncomprises an anionic surfactant. A process for preparing a compositionfor inhibiting dental erosion comprising the steps of adding an aqueoussolution of hydrofluoric acid in a concentration of 0.05-2.00% is alsocomprised in the present invention. The pH of the aqueous solution isbetween 2.5 and 4.5. The composition comprises at least one of ahumectant, a binder, a thickening agent, one or several abrasive agents,a liquid phase including a humectant, a surfactant and flavour. Further,said abrasive agents is any one of silica, xerogels, hydrogels andaerogels, and said abrasive agent is silica in a concentration of 3%-75%by weight. The liquid phase according to the present invention,comprises said humectant in a concentration of 10-90% by weight of thecomposition. The humectant is chosen, from cellulose, xanthan gum,sorbitol, glycerol, propylene glycol, polypropylene and polyethyleneglycol. Further, the binder and said thickening agent is any one ofsodium carboxymethyl cellulose, hydroxyethyl cellulose, xanthan gumfinely divided silica, Irish moss and synthetic hectorities in aconcentration of 0.5-10% by weight of the composition. The surfactant isan anionic surfactant.

The present invention describes use of a composition comprising aqueoussolutions of hydrofluoric acid in a concentration of 0.05-2.00% forinhibiting dental erosion.

It has now been found that dental compositions consisting of dilutedhydrofluoric acid pH 2.5-4.5 decrease the solubility of dental enamel inerosive acids (hydrochloric acid at pH 2.2 or citric acid pH 3.5)markedly (to 80% or more), even after a brief exposure of human teeth tothe said compositions, before subsequent exposure to erosive acids. Thisshows that these compositions provide protection even against severedental erosions caused by eating disorder whereby strong HCl may reachthe oral cavity and the teeth. These compositions also protect againstany organic or inorganic weak acids which may be present in beverages orfruits. The compositions include dentifrices, gels for topicalapplication, lozenges and liquids. The maximum amounts of fluorideneeded in the said compositions are the conventional concentrations usedin such compositions, but dental hard tissues (enamel, dentine andcementum) are known to be highly soluble in erosive acids. Theobservations leading to the present invention were thus totallyunexpected.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 describes solubility reduction of teeth in aqueous solutions.

FIG. 2 describes solubility reduction of enamel.

FIG. 3 describes solubility reduction of dentine.

FIG. 4 describes solubility reduction of cementum.

DETAILED DESCRIPTION

Aqueous solutions of hydrofluoric acid (HF) are a weak acid whichbuffers between pH 3 and 4 and has a pK_(a) of 3.45. The presentinvention is based on the observation that HF between pH 3 and pH 4 hasunique properties by providing dental mineral tissues (i.e. enameldentine and cementum) with a surface layer which forms immediately, andprotects the mineralized tissues against erosive acids. This layerconsists of calcium fluoride-like material which is particularlyresistant against erosive acids. Possibly because it is formed underacidic condition. In the experiments concerning this effect we have usedsevere erosive challenges to ascertain that this was a clinicallysignificant effect. The erosive challenge was 0.1M citric acid of pH2.2, for 30 min., and human teeth were used. In vivo it is known thathuman saliva can neutralize acids, and that proteins adsorbed to teethwill protect the dental surfaces to some degree, against erosive acids.No attempts to mimic these protective forces were included, and it isbelieved that the experimental conditions used are more severe than mostclinical challenges.

Because of the buffering capacity of aqueous solutions of HF, theformation of the protective layer is formed at low pH, which appears tobe favourable. It is furthermore believed that un-dissociated HF has theability to come closer to the charged enamel surface than chargedspecies of F. Un-dissociated HF can probably interact with the toothsurface by ionic exchange without, (or with a minimum of), free protons,which could etch and cause damage to the tooth surface. This conceptwould indicate that the region below the pK_(a) is of particularsignificance for the unique effect of aqueous HF.

The oral compositions of the present invention may contain orallyacceptable ingredients in conventional amounts, depending upon the finalform of the composition, i.e. whether a dentifrice a gel or a lozenge. Adentifrice will usually comprise an abrasive agent cleaning agent in anamount of from 3-75% by weight. Suitable abrasive cleaning agents areparticulate aluminas, silica, xerogels, hydrogels and aerogels, andprecipitated particulate silicas, calcium pyrophosphate, insolublesodium metaphosphate, calcium carbonate, dicalcium orthophosphate andseveral others.

Dentifrices usually contain liquid phase comprising water and humectantsin amounts of 10-99% by weight. Typical humectants are sorbitol,glycerol, propylene glycol, polypropylene glycol and many others.

A wide variety of thickening agents or binders are used in dentifricesincluding sodium carboxyl methyl cellulose, hydroxyethyl cellulose,finely devided silica, xanthan gum, Irish moss and synthetic hectorites.The amount of binders will usually range from 0.5-10% by weight of thedentifrice.

A further conventional ingredient of a dentifrice is an organicsurfactant. Anionic surfactant is usually preferred because of theirgood foaming properties. Sodium lauryl sulphate is usually chosen, butan alkyl aryl sulphates, especially sodium dodecyl benzene sulphonatecan be used in the present invention.

Various optional ingredient may be included of the invention includingflavouring agents, sweetening agent such as sodium saccharin, andwhitening agent such as titanium dioxide, anti-plaque agents, and agentsfor adjusting the pH of the dentifrice, which may range from 2.8-4.5.Such agents for acidification includes citric-, acetic- or maleic acidsand their buffers. Weak inorganic acids such as phosphoric or fluorideacids, and strong acids as hydrochloric acid and its buffers.

A gel for topical application according to the present invention maycontain from 1% to 0.1% F⁻, depending on whether the gel is designed forweekly or daily use. The gel contain a thickening agent such as watersoluble salts such as sodium carboxy methyl cellulose. Natural gums likegum arabic can also been used as thickeners in gels. The concentrationof thickener is usually from 1-2%. A sweetening agent like xylitol orsaccharin can be added in amounts of 5-10% or 0.2-0.3%, respectively,and a flavouring agent.

A lozenge according to the present invention should contain 0.25 mg Fand 100 mg of citric acid, and in addition 400 mg of xylitol, aflavouring agent and necessary constituents up to 0.6 g.

Experiment

Extracted teeth were cleaned and pre-treated for 5 min with 0.01% HCl toeliminate differences in solubility between the individual teeth, andthen treated with diluted hydrofluoric acid. The teeth (usually 6parallels) were then exposed to 0.1M citric acid or 0.01% HCl for 30min, and the release of calcium into the acid measured by atomicabsorption. The teeth treated with hydrofluoric acid were compared withcontrol teeth (usually 6) which were only exposed to water. The resultsare given in FIG. 1. It can be seen that treatment with 0.1%hydrochloric acid gave a solubility reduction of 20% of the control,whereas 1% hydrochloric acid gave a solubility reduction of close to80%. Teeth treated with 0.4% of stannous fluoride was included forcomparison. FIG. 1 shows the results of whole teeth treated with 0.01MHCl, whereas FIGS. 2, 3 and 4 shows the result of etching with 0.1%citric acid on enamel, dentine and cementum. Treatment with lowconcentrations of aqueous solutions of HF cause major reductions insolubility of the tooth samples. This example demonstrates that dilutedhydrofluoric acid (0.1-1.0%) reduces the solubility of enamel (see FIG.2), Dentine (see FIG. 3) and cementum (see FIG. 4) in 0.1M citric acid.

The teeth were cut in two at the enamel cementum junction and theexposed dentine covered by acid resistant varnish. Dentin samples wasmade by removing enamel from tooth crowns and varnished as describedabove. The experiments were performed in 6 parallels. The tooth sampleswere first exposed to 0.1M citric acid for 30 min. The teeth were thenwashed in distilled water and dried, and then treated with therespective dilutions of hydrofluoric acid for 10 min. The teeth wereindividually treated and each tooth served as its own control. The teethwere again washed and dried and then treated with 0.1M citric acid forthe second time.

The solubility of the tooth samples was assessed by measuring theconcentration of calcium in the citric acid. A reduction in calciumconcentration between the first and second citric acid samples wasassumed to be caused by the profylactic treatment with hydrofluoric aciddilutions.

It can be seen from the figures that 0.1% of HF caused about 45%reduction in the solubility of enamel (FIG. 2), 80% reduction in dentinesolubility (FIG. 3), and 95% reduction of cementum solubility (FIG. 4).0.2% HF reduced the solubility 90%, 90% and 95% respectively.

It can thus be seen that very low concentrations of HF have majoreffects on solubility. (0.1% HF represents 1 part of 40% HF in 399 partsof water and its application on teeth represents no health hazard.

Example 1

A gel having the following composition was made:

Ingredient % Silica thickener   50% Xanthan gum  0.1% Sodium saccharin0.23% Xylitol   5% Cardemom oil   1% Hydrofluoric acid  0.3% Water ad 100%

Example 2

A dentifrice having the following composition was made:

Silica abrasive   60% Sorbitol syrup (70% sol)   25% Xanthan gum   1%Sodium saccharide 0.25% Sodium lauryl sulfate  1.0% Flavour (Cardedmomoil)  1.0% Hydrofluoric acid  0.1% Water add  100%

Example 3

A toothpaste according to the present invention (%)

-   Silica Abrasives: 56-   Sorbitol (70% sol): 21-   Sodium lauryl sulphate 1.5-   Xanthan gum: 0.875-   Titan dioxide: 0.5-   HCl(37%): 0.15-   F⁻: 0.15%-   Citric buffer pH 3.0, 0.1 M add 100

The invention claimed is:
 1. A composition with active agent forinhibiting dental erosion, the composition consisting essentially ofhydrogen fluoride, and at least one of a humectant, a binder athickening agent, an abrasive agent, a surfactant and a flavoring agent,wherein the hydrogen fluoride is the only fluoride present and ispresent in an aqueous solution at a concentration of 0.1-1% (w/v), thepH of the aqueous solution being between 2.5 and 4.5, and wherein theactive agent is un-dissociated hydrogen fluoride.
 2. The compositionaccording to claim 1, wherein said abrasive agent is present and isselected from the group consisting of silica, xerogels, hydrogels andaerogels.
 3. The composition according to claim 2, wherein said abrasiveagent is silica in a concentration of 3-75% by weight.
 4. Thecomposition according to claim 1, wherein said humectant is present andis selected from the group consisting of cellulose, xanthan gum,sorbitol, glycerol, propylene glycol, polypropylene and polyethyleneglycol.
 5. The composition according to claim 1, wherein said binder andsaid thickening agent are present in a concentration of 0.5-10% byweight of the composition.
 6. The composition according to claim 1,wherein said surfactant is present and is an anionic surfactant.
 7. Acomposition for inhibiting dental erosion according to claim 1 in theform of a dentifrice.
 8. A composition for inhibiting dental erosionaccording to claim 1 in the form of a gel.
 9. A dentifrice with activeagent for inhibiting dental erosion of teeth caused by organic acids,the dentifrice consisting essentially of a liquid phase that is 10-99%by weight of water and humectants, and hydrogen fluoride as the onlyfluoride present, wherein the hydrogen fluoride present at aconcentration of 0.1-1% (w/v), wherein the pH of the dentifrice isbetween 2.8 and 4.5, and wherein the active agent is un-dissociatedhydrogen fluoride.
 10. The dentifrice according to claim 9, wherein saidliquid phase comprises said humectant in a concentration of 10-90% byweight of the dentifrice.
 11. A gel composition with active agent forinhibiting dental erosion, the gel composition consisting essentially of(a) 1-2% of a thickening agent; (b) optionally one or more of asweetening agent and a flavoring agent; and (c) hydrogen fluoride as theonly fluoride present at a concentration of 0.1-1% (w/v), wherein the pHof the aqueous solution is between 2.5 and 4.5, and wherein the activeagent is un-dissociated hydrogen fluoride.